Heterochromatin and the phenomenon of chromosome banding.
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Animals↗
Biomedical subjects
B Hamilton
Publications and source records attributed to B Hamilton.
Relationship between cellular RecA protein concentration and untargeted mutagenesis in Escherichia coli.
We measured the production of untargeted mutations in the cI and cII genes of untreated lambda phage undergoing a lytic cycle in UV-irradiated bacterial hosts. As previously shown, treatment with 4 micrograms/ml of rifampicin during post-irradiation incubation inhibited amplification of the RecA protein in these cells. In addition, we observed a decreased mutation rate compared to the untreated, irradiated bacteria. Treatment with 4 micrograms/ml or 8 micrograms/ml rifampicin did not prevent the UV induction of the umuDC operon, as judged by assay of beta-galactosidase activity in a umuC-lacZ fusion strain. In contrast, the UV-induction of beta-galactosidase in the sulA-lacZ fusion strain was decreased by 4 micrograms/ml rifampicin. The inhibition of untargeted mutagenesis by this drug treatment was also observed in a strain constitutive for SOS functions (lexA (Def)) as well as in a RecA-overproducing plasmid strain, suggesting the requirement of other factor(s) in wild-type recA+ cells. An htpR165-carrying strain, that blocks induction of heat-shock proteins, exhibited normal UV-promoted mutagenesis. A correlation was observed between the cellular concentration of RecA protein, increased spontaneously by a temperature shift in a lexA(Ts) strain, and the extent of UV-promoted untargeted mutagenesis. These results suggest a mechanistic role of RecA protein in this process.
Bacterial Proteins↗
Munchausen syndrome by proxy.
Munchausen syndrome by proxy is a form of child abuse in which a disorder of the child is fabricated by a parent. Although often considered rare, it may have been overlooked frequently in the past. The reported cases of children with Munchausen syndrome by proxy range in age from infancy to 8 years. Their "illnesses" consist of fabricated histories, inflicted physical findings, altered laboratory specimens, and induced disorders. The perpetrator usually is the child's mother, who may have Munchausen syndrome. Consequences of the syndrome may include painful tests, frequent hospitalizations, potentially harmful treatment, and death. The diagnosis can be made when medical and social histories are characteristic of the syndrome and clinical findings are absent, suggestive of induced illness, or resolve upon separation of the child and parent. Suspicion of the syndrome should be discussed with the family once the safety of the child is insured, and the case should be reported under the child abuse reporting law of the state. Social, family, and medical histories must be obtained and verified, and court intervention should be considered. Four patients who illustrate typical features of the syndrome are described.
Child↗
Use of a "pneumatic" tube in anatomic pathology.
In anticipation of the temporary relocation of Surgical Pathology some distance from the operating rooms, a "pneumatic" tube system was installed to transport fresh tissue from surgery to pathology at the Hospital of the University of Pennsylvania. The point-to-point 4-inch internal diameter system is actually of the blower or "pea-shooter" type. Side-opening carriers were preferred, and electronic sensors were installed for monitoring and safety. At the pathology end of the system, a complete panel of electrical controls exist that are capable of initiating the blower at either end, enabling full control. For possible future retrieval of stuck carriers, several points of mechanical entry were desired and constructed. The transit time over 886 feet varies with the weight of the specimen but averages 25-35 seconds. Thus far, after 32 months and 12,652 transits, no specimens have been lost or damaged. During the first few months, two specimens became stuck for reasons relating to human error but were easily retrieved. This system, in conjunction with operating room telephone intercoms, has become fully accepted and trusted by surgeons and pathologists.
Biopsy↗
High school students' long-term retention of sex education information.
Ninth grade students in a rural South Carolina school were pretested about sexuality information, completed a 12-unit reproductive health course in eight months, and were posttested. A control group received the same pretest and posttest. Both groups were retested after the 10th and 11th grades and mean scores were calculated and compared. The difference between the experimental group's pretest and posttest mean scores was 8.49 (p less than .001); the difference between the control group's pretest and posttest mean scores was 1.0 (p = .003). The experimental group's mean score remained at least 5.2 points higher (p less than .001) than the control group's score on the same test one and two years after the course. Comparison of the mean gain between the pretest and posttest scores, and between the pretest and fourth test scores, confirmed the results obtained by mean test scores. The test scores indicated that the knowledge of the experimental students increased significantly and was sustained for two years. Their scores remained significantly higher than those of the control group on the posttest, and on tests one and two years later.
Adolescent↗
Clinical trial of the efficacy and safety of ticarcillin and clavulanic acid.
Forty-three hospitalized patients were treated with a new antibiotic combination containing ticarcillin plus the beta-lactamase inhibitor, clavulanic acid, in a fixed combination for intravenous use. A variety of infections were treated, including pneumonia, bacteremia, urinary tract infection, and osteomyelitis. Of 50 episodes of infection in 43 patients, 44 clinical cures were obtained, with 5 patients improving and 1 patient failing to respond to treatment. In vitro susceptibility testing of 101 clinical isolates was notable for the rarity of resistance to the combination antibiotic. Of specific interest, all 14 isolates of Staphylococcus aureus were susceptible to ticarcillin plus clavulanic acid, whereas only 2 of the 14 isolates were susceptible to ticarcillin alone. Adverse reactions to the study drug were minimal; eosinophilia, unaccompanied by other allergic phenomena, and oral candidiasis were most frequent. Overall, the combination of ticarcillin with the beta-lactamase inhibitor, clavulanic acid, appears to be a safe and effective drug for the treatment of infections caused by susceptible organisms.
Aged↗
Lethal graft-versus-host disease: modification with allogeneic cultured donor cells.
The use of the bone marrow culture technique was studied as a means to prepare donor marrow for bone marrow transplantation to avoid lethal graft-versus-host disease (GVHD). Preliminary experiments demonstrated the rapid loss of theta-positive cells in such cultures, so that theta-positive cells were not detected after 6 days. Initial experiments in C3H/HeJ (H-2k, Hbbd) recipients prepared with 900 rad demonstrated improved survival when 3-day cultured C57BL/6 (H-2b, Hbbs) donor cells were used in place of hind limb marrow for transplantation. However, hemoglobin typing of recipient animals revealed only short-term donor engraftment, with competitive repopulation of recipient marrow occurring. Subsequent experiments were done in 1,200-rad prepared recipients, with long-term donor engraftment demonstrated. The majority of 1,200-rad prepared animals receiving cultured allogeneic cells died of GVHD, but animals receiving 28-day cultured cells had an improved 90-day survival and a delay in GVHD development over animals receiving hind limb marrow or marrow from shorter times in culture. In addition, animals receiving anti-theta-treated, 3-day nonadherent cells had an improved survival (44%) over animals receiving anti-theta-treated hind limb marrow (20%). These experiments demonstrate modest benefit for the use of cultured cells in bone marrow transplantation across major H-2 histocompatibility complex differences.
Animals↗
Generation of cytolytic T lymphocytes in thymectomized, irradiated, and bone marrow-reconstituted mice.
A model system has been developed to study extrathymic T cell differentiation. Mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1-positive cells. After 8 wk, the spleen cells of these 5athymic, bone marrow-reconstituted chimeras contain Thy-1-positive pre-cytolytic T lymphocytes (CTL) that are able to respond to antigen only when exogenous interleukin 2 is added to culture.. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be an immature T cell. Initial evaluation of the CTL repertoire of these athymic mice demonstrates that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2 restricted and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal but not in nude mice. The discrepancies observed in the CTL repertoire between these thymectomized chimeras and nude mice are discussed.
Animals↗
Pindolol: effects on blood pressure and plasma renin activity.
The influence of pindolol, other antihypertensive agents, or placebo upon plasma renin activity (PRA) was examined in five separate studies involving 249 subjects (pindolol), n = 149; propranolol, n = 43; methyldopa, n = 13; chlorthalidone, n = 16; placebo, n = 28). In addition, the subjects were stratified in for studies into low (n = 104), medium (n = 96), or high (n = 15) PRA categories according to baseline PRA and sodium excretion measurements. The response to antihypertensive therapy was analyzed in each PRA category. Pindolol and propranolol lowered PRA comparably at equivalent dosages, although this effect was not consistently observed in all studies or at all dosage levels. Methyldopa therapy was not associated with a decline in PRA and chlorthalidone elevated PRA. Pindolol and propranolol lowered both supine and erect diastolic blood pressure (BP) comparably. This effect was similar in subjects categorized as having low or medium PRA. Too few patients were studied with high PRA to derive statistically meaningful data. Pindolol lowered standing systolic BP to a greater extent than did propranolol, especially in the medium PRA category. It was concluded that pindolol, like other beta-adrenergic blockers, lowers PRA, that the effect of pindolol on diastolic BP is independent of the baseline PRA category, and that pindolol is more effective than propranolol in lowering standing systolic BP, at least in the medium PRA category.
Adult↗
Long-term intermittent catheterization in the spinal cord injury patient.
Intermittent catheterization was used as a means of long-term bladder management in 85 patients with spinal cord injury. Of these patients followup data revealed that 28 (33 per cent) had reflux and/or hydronephrosis. Treatment in 15 patients consisted of increasing the frequency of catheterization to every 4 hours and avoiding high fluid intake during a relative short interval. Sphincterotomy was done in 3 patients, while 10 were placed on an indwelling catheter because of an inability to adapt to or refusal of other forms of treatment. The upper urinary tract changes noted seemed to be related to increased intravesical pressure, either from too long an interval between catheterizations or from marked detrusor hyperreflexia with sphincter obstruction. Close followup seems necessary in these patients.
Adult↗
Translational control of catalase synthesis by hemin in the yeast Saccharomyces cerevisiae.
mRNA-dependent cell-free protein synthesis systems were prepared from a heme-deficient ole3 mutant of the yeast Saccharomyces cerevisiae grown either in the absence or in the presence of the heme precursor delta-aminolevulinate. When supplemented with total yeast mRNA, the two systems-from heme-deficient and from heme-containing cells-translate most mRNAs with comparable efficiencies. mRNAs coding for the hemoproteins catalase T and catalase A, however, are translated at a low rate by the system from heme-deficient cells whereas their translation in the system from heme-containing cells is comparable to that observed in a heterologous in vitro system from wheat germ. Addition of 10 muM hemin to the system from heme-deficient cells stimulates translation of catalase mRNAs significantly. Control experiments showed that the results obtained cannot be explained by specific proteinase or nuclease action. Together with previous findings indicating lack of translation of catalase T mRNA in heme-deficient cells in vivo, the results demonstrate that specific control of yeast catalase formation occurs at the level of translation.
Catalase↗
Preparation of a mRNA-dependent cell-free translation system from whole cells of Saccharomyces cerevisiae.
A cell-free protein-synthesizing system has been prepared from Saccharomyces cerevisiae by mechanical breakage of cells, isolation of a 30000 x g supernatant fraction and removal of endogenous mRNA by treatment with micrococcal nuclease. The system thus isolated is dependent on added mRNA and translates yeast mRNA to discrete products, many of then identical with yeast proteins synthesized in vivo. Activity and properties of this system are comparable to those of other eukaryotic cell-free translation systems. It offers the following advantages, compared to yeast translation systems described previously. (a) Its isolation is simple and fast. (b) Since it is not isolated from spheroplasts there is no danger of its inactivation by contaminants in enzymes used for spheroplast preparation. (c) Isolation appears to be less strain-dependent and can be carried out starting from cells in various physiological states.
Cell-Free System↗
Regulation of synthesis of catalases and iso-1-cytochrome c in Saccharomyces cerevisiae by glucose, oxygen and heme.
The regulation of the hemoproteins catalase T, catalase A and iso-1-cytochrome c was studied in the yeast Saccharomyces cerevisiae. Levels of catalase T and catalase A mRNAs are low or undetectable in anaerobic and heme-deficient cells, and in wild type strains grown on high glucose concentrations. Regulatory mutants (cgr4 and cas1), which have previously been shown to have high catalase T activity when grown in the absence of oxygen or on high glucose concentrations, have high levels of catalase T mRNA when grown under glucose repression conditions. Whereas no catalase T mRNA could be detected in a heme-deficient (ole3) single mutant, double mutants (ole3 cgr4) and (ole3 cas1) contain mature catalase T mRNA. Catalase T and A mRNAs are accumulated rapidly during adaptation of anaerobic cells to oxygen. Anaerobic and heme-deficient cells lack or have extremely low levels of iso-1-cytochrome c mRNA, which, like catalase mRNAs, is accumulated rapidly during oxygen adaptation. The results obtained demonstrate that glucose, oxygen and heme regulate the synthesis of the hemoproteins studied by controlling mRNA levels. In addition, posttranscriptional, probably translational control has to be postulated at least in the case of catalases, to explain the results obtained.
Catalase↗
Receptor binding and processing of epidermal growth factor by human breast cancer cells.
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Breast Neoplasms↗
The anovulatory hamster: a comparison of the effects of short photoperiod and daily melatonin injections on the induction and termination of ovarian acyclicity.
Cyclic female hamsters were rendered anovulatory by daily subcutaneous melatonin injections (25 microgram/0.1 ml oil) in 29 days or by transfer to a short light cycle, LD 6:18 (lights 1000-1600 hrs) in 33 days. Estrous cyclicity was reinitiated in these animals in 44 or 45 days following cessation of melatonin injections or transfer to long light cycles (LD 14:10, lights 0600-2000 hrs), respectively. Exposure of both groups to LD 6:18 after reinitiation of estrous cyclicity caused a second cessation of ovulation in 75 (melatonin group) or 61 (short light cycle group) days. Thus, although both treatments disrupted estrous cyclicity for nearly 6 weeks, this was not sufficient to induce photorefractoriness (failure to respond to short light cycles with continued estrous cyclicity). Rather, every animal responded to LD 6:18 and ceased ovulating. Melatonin-induced anovulatory hamsters showed daily gonadotropin release patterns identical to those reported in hamsters in other anovulatory states (lactating, prepubertal, and photoinduced anovulatory hamsters); that is, peak LH and FSH release at 1700 hrs daily.
Animals↗
Antagonism between epidermal growth factor and phorbol ester tumor promoters in human breast cancer cells.
It has been suggested that the phorbol ester tumor promoters act via the receptor-effector system for epidermal growth factor (EGF), since they interact with the EGF receptor system and mimic many of the effects of EGF in cultured cells. We have studied the interaction of phorbol esters with the EGF-responsive MCF-7 human breast cancer cell line. Similar to other systems, phorbol esters inhibit EGF binding in MCF-7 cells in a manner paralleling their potency as tumor promoters in mice. The effect is specific for EGF since the membrane binding of insulin is unaffected. Like EGF, the potent phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) stimulates protein synthesis as indicated by a twofold increase in [(3)H]leucine incorporation into protein after 24 h in TPA. Cell morphology, however, is significantly different with TPA treatment. After 24-48 h in TPA, cells become markedly enlarged with increased cytoplasmic vacuolization and increased membrane microvilli. This is reflected in a fourfold increase in the protein/DNA ratio (control 13.1; TPA 55.9). Furthermore, TPA inhibits cell division in media with or without serum, and prevents growth stimulation by EGF. Low TPA concentrations (1.0 ng/ml) are active, and 10 ng/ml results in maximal inhibition of cell replication. Other phorbol esters inhibit MCF-7 cells relative to their tumor promoting activity in vivo and their ability to inhibit EGF binding in these cells. After 24 h in TPA, incorporation of [(3)H]thymidine into DNA is markedly reduced and the thymidine labeling index falls (33% to 2%) indicating very few S-phase cells. Growth inhibition is reversible by removing TPA from the medium. Similar inhibitory effects are seen with the two other human breast cancer cell lines studied, ZR75-1 and MDA-MB-231. In conclusion, phorbol esters may interact with the EGF receptor domain in MCF-7 human breast cancer cells, but they have distinct effects on cell morphology and growth suggesting alternative pathways of action. The antineoplastic activity of these compounds needs further investigation.
Breast Neoplasms↗
Clonidine after renal ischemia to lessen acute renal failure and microvascular damage.
Clonidine, an antihypertensive drug that inhibits renin release and causes a water diuresis in normal animals, was tested for its ability to reduce the severity of post-ischemic acute renal failure produced in rabbits by clamping the left renal pedicle for 1 hour and removing the opposite kidney. Clonidine significantly lessened renal failure when given during, or 1 hours after, the ischemic insult in dehydrated rabbits. It was also effective when given during the ischemic insult in vasopressin-treated water-drinking rabbits but not in control water-drinking rabbits. In vasopressin-treated rabbits, clonidine lessened renal failure observed 2 days after the ischemic insult despite the fact that in the immediate postischemic period it lowered total renal blood flow, produced hypotension, and did not bring about lower plasma renin levels. Clonidine treatment resulted in less outer medullary microvascular damage (demonstrated by colloidal carbon staining), higher outer medullary blood flow 1 to 2 hours after unclamping, fewer casts, and higher creatinine clearance and free water clearance/creatinine clearance 4 to 6 hours after unclamping compared with controls. The effect of clonidine was unrelated to plasma renin activity. Clonidine did not alter plasma vasopressin concentration. Demeclocycline and lithium, two agents that blunt renal responsiveness to vasopressin, had a beneficial effect in dehydrated animals similar to that of clonidine, but the angiotensin II antagonist saralasin and the angiotensin converting enzyme inhibitor SQ20881 did not. Normal rabbits given a large dose of vasopressin in oil plus clonidine had significantly greater urine output and free water clearance and lower urine osmolality than did rabbits given vasopressin in oil alone. These results suggest that clonidine may be beneficial because it prevents ischemic microvascular injury in the renal outer medulla, an effect that may decrease tubular obstruction by lessening desquamation of damaged tubular cells or cell constituents into the tubular lumen. Clonidine may also decrease formation of obstructive hyaline casts in collecting ducts by blunting the kidney's response to vasopressin and increasing tubular fluid flow rate.
Acute Kidney Injury↗